Henry MarkramHenry Markram started a dual scientific and medical career at the University of Cape Town, in South Africa. His scientific work in the 80s revealed the polymodal receptive fields of pontomedullary reticular formation neurons in vivo and how acetylcholine re-organized these sensory maps.
He moved to Israel in 1988 and obtained his PhD at the Weizmann Institute where he discovered a link between acetylcholine and memory mechanisms by being the first to show that acetylcholine modulates the NMDA receptor in vitro studies, and thereby gates which synapses can undergo synaptic plasticity. He was also the first to characterize the electrical and anatomical properties of the cholinergic neurons in the medial septum diagonal band.
He carried out a first postdoctoral study as a Fulbright Scholar at the NIH, on the biophysics of ion channels on synaptic vesicles using sub-fractionation methods to isolate synaptic vesicles and patch-clamp recordings to characterize the ion channels. He carried out a second postdoctoral study at the Max Planck Institute, as a Minerva Fellow, where he discovered that individual action potentials propagating back into dendrites also cause pulsed influx of Ca2 into the dendrites and found that sub-threshold activity could also activated a low threshold Ca2 channel. He developed a model to show how different types of electrical activities can divert Ca2 to activate different intracellular targets depending on the speed of Ca2 influx an insight that helps explain how Ca2 acts as a universal second messenger. His most well known discovery is that of the millisecond watershed to judge the relevance of communication between neurons marked by the back-propagating action potential. This phenomenon is now called Spike Timing Dependent Plasticity (STDP), which many laboratories around the world have subsequently found in multiple brain regions and many theoreticians have incorporated as a learning rule. At the Max-Planck he also started exploring the micro-anatomical and physiological principles of the different neurons of the neocortex and of the mono-synaptic connections that they form - the first step towards a systematic reverse engineering of the neocortical microcircuitry to derive the blue prints of the cortical column in a manner that would allow computer model reconstruction.
He received a tenure track position at the Weizmann Institute where he continued the reverse engineering studies and also discovered a number of core principles of the structural and functional organization such as differential signaling onto different neurons, models of dynamic synapses with Misha Tsodyks, the computational functions of dynamic synapses, and how GABAergic neurons map onto interneurons and pyramidal neurons. A major contribution during this period was his discovery of Redistribution of Synaptic Efficacy (RSE), where he showed that co-activation of neurons does not only alter synaptic strength, but also the dynamics of transmission. At the Weizmann, he also found the tabula rasa principle which governs the random structural connectivity between pyramidal neurons and a non-random functional connectivity due to target selection. Markram also developed a novel computation framework with Wolfgang Maass to account for the impact of multiple time constants in neurons and synapses on information processing called liquid computing or high entropy computing.
In 2002, he was appointed Full professor at the EPFL where he founded and directed the Brain Mind Institute. During this time Markram continued his reverse engineering approaches and developed a series of new technologies to allow large-scale multi-neuron patch-clamp studies. Markrams lab discovered a novel microcircuit plasticity phenomenon where connections are formed and eliminated in a Darwinian manner as apposed to where synapses are strengthening or weakened as found for LTP. This was the first demonstration that neural circuits are constantly being re-wired and excitation can boost the rate of re-wiring.
At the EPFL he also completed the much of the reverse engineering studies on the neocortical microcircuitry, revealing deeper insight into the circuit design and built databases of the blue-print of the cortical column. In 2005 he used these databases to launched the Blue Brain Project. The BBP used IBMs most advanced supercomputers to reconstruct a detailed computer model of the neocortical column composed of 10000 neurons, more than 340 different types of neurons distributed according to a layer-based recipe of composition and interconnected with 30 million synapses (6 different types) according to synaptic mapping recipes. The Blue Brain team built dozens of applications that now allow automated reconstruction, simulation, visualization, analysis and calibration of detailed microcircuits. This Proof of Concept completed, Markrams lab has now set the agenda towards whole brain and molecular modeling.
With an in depth understanding of the neocortical microcircuit, Markram set a path to determine how the neocortex changes in Autism. He found hyper-reactivity due to hyper-connectivity in the circuitry and hyper-plasticity due to hyper-NMDA expression. Similar findings in the Amygdala together with behavioral evidence that the animal model of autism expressed hyper-fear led to the novel theory of Autism called the Intense World Syndrome proposed by Henry and Kamila Markram. The Intense World Syndrome claims that the brain of an Autist is hyper-sensitive and hyper-plastic which renders the world painfully intense and the brain overly autonomous. The theory is acquiring rapid recognition and many new studies have extended the findings to other brain regions and to other models of autism.
Markram aims to eventually build detailed computer models of brains of mammals to pioneer simulation-based research in the neuroscience which could serve to aggregate, integrate, unify and validate our knowledge of the brain and to use such a facility as a new tool to explore the emergence of intelligence and higher cognitive functions in the brain, and explore hypotheses of diseases as well as treatments.
Mikhail ChuraevBorn in 1995 in Moscow, Russia. Bachelor and Master degree obtained at Moscow Institute of Physics and Technology (MIPT) in 2016 and 2018. The second Master degree obtained at Skolkovo Institute of Science and Technology (Skoltech) in 2018.Mikhail joined the lab in March 2019 as a PhD student.
Viacheslav SnigirevViacheslav Snigirev was born in 1996 in Moscow. As a holder of the 1st rank degree in Lomonosov Olympiad in Physics 2014 and of the golden medal for the academic achivements in high school, he was accepted to Lomonosov Moscow State University as a bachelor student of the Department of Physics in the same year. In 2018 he defended his bachelor thesis Ultrafast dynamics of light scattering in direct-bandgap semiconductor nanoparticles under supervision of Prof. Andrey A. Fedyanin and Dr. Alexander S. Shorokhov. He then continued to carry out research under their supervision in the area of active all-dielectric metaphotonics and joined the master program Quantum Electronics and Quantum Optics at the same university, finishing it in 2020 with the master thesis title Photo- and electrically induced modulation of optical response of Mie-resonant gallium arsenide nanoparticles and metasurfaces. The both degrees are degrees with honours containing only excellent grades. The scientific results obtained within the framework of his bachelor and master programs were presented on international conferences CLEO Europe and METANANO.
Nicolai CramerNicolai Cramer was born in Stuttgart, Germany; he studied chemistry at the University of Stuttgart where he graduated in 2003, and earned his PhD in 2005 under the guidance of Professor Sabine Laschat. After a research stage at Osaka University, Japan, he joined the group of Professor Barry M. Trost at Stanford University as a postdoctoral fellow in 2006. From 2007 on, he worked on his habilitation at the ETH Zurich associated to the chair of Professor Erick M. Carreira and recieved the venia legendi in 2010. In 2010, he started as Assistant Professor at the EPF Lausanne and was promoted to Associate Professor in 2013 and to Full Professor in 2015. His main research program encompasses enantioselective metal-catalyzed transformations and their implementation for the synthesis of biologically active molecules.
Author profile (Angew. Chem. Int. Ed.)
CV
Philippe GilletPhilippe GILLET completed his undergraduate studies in Earth Science at Ecole normale supérieure de la rue dUlm (Paris). In 1983 he obtained a PhD in Geophysics at Université de Paris VII and joined Université de Rennes I as an assistant. Having obtained a State Doctorate in 1988, he became a Professor at this same university, which he left in 1992 to join Ecole normale supérieure de Lyon.
The first part of his research career was devoted to the formation of mountain ranges particularly of the Alps. In parallel, he developed experimental techniques (diamond anvil cells) to recreate the pressure and temperature prevailing deep inside planets in the lab. These experiments aim at understanding what materials make up the unreachable depths of planets in the solar system.
In 1997, Gillet started investigating extraterrestrial matter. He was involved in describing meteorites coming from Mars, the moon or planets which have disappeared today and explaining how these were expelled from their original plant by enormous shocks which propelled them to Earth. He also participated in the NASA Stardust program and contributed to identify comet grains collected from the tail of Comet Wild 2 and brought back to Earth. These grains represent the initial minerals in our solar system and were formed over 4.5 billion years ago. He has also worked on the following subjects:
Interactions between bacteria and minerals.
Solid to glass transition under pressure.
Experimental techniques: laser-heated diamond anvil cell, Raman spectroscopy, X-ray diffraction with synchrotron facilities, electron microscopy.
Philippe Gillet is also active in science and education management. He was the Director of the CNRS Institut National des Sciences de lUnivers (France), the President of the French synchrotron facility SOLEIL and of the French National Research Agency (2007), and the Director of Ecole normale supérieure de Lyon. Before joining EPFL he was the Chief of Staff of the French Minister of Higher Education and Research.
Selected publications:
Ferroir, T., L. Dubrovinsky, A. El Goresy, A. Simionovici, T. Nakamura, and P. Gillet (2010), Carbon polymorphism in shocked meteorites: Evidence for new natural ultrahard phases, Earth and Planetary Science Letters, 290(1-2), 150-154.
Barrat J.A., Bohn M., Gillet Ph., Yamaguchi A. (2009) Evidence for K-rich terranes on Vesta from impact spherules. Meteoritics & Planetary Science, 44, 359374.
Brownlee D, Tsou P, Aleon J, et al. (2006) Comet 81P/Wild 2 under a microscope. Science, 314, 1711-1716.
Beck P., Gillet Ph., El Goresy A., and Mostefaoui S. (2005) Timescales of shock processes in chondrites and Martian meteorites. Nature 435, 1071-1074.
Blase X., Gillet Ph., San Miguel A. and Mélinon P. (2004) Exceptional ideal strength of carbon clathrates. Phys. Rev. Lett. 92, 215505-215509.
Gillet Ph. (2002) Application of vibrational spectroscopy to geology. In Handbook of vibrational spectroscopy, Vol. 4 (ed. J. M. Chalmers and P. R. Griffiths), pp. 1-23. John Wiley & Sons.
Gillet Ph., Chen C., Dubrovinsky L., and El Goresy A. (2000) Natural NaAlSi3O8 -hollandite in the shocked Sixiangkou meteorite. Science 287, 1633-1636.
